Apparatus and Method for Ocular Treatment

ABSTRACT

The invention provides tools, materials and related methods to surgically access the suprachoroidal space of an eye for the purpose of performing minimally invasive surgery or to deliver drugs to the eye. The invention provides a flexible microcannula device ( 11, 13 ) that may be placed into the suprachoroidal space ( 12, 14 ) through a small incision ( 12 A) of the overlying tissues, maneuvered into the appropriate region of the space, and then activated to treat tissues adjacent to the distal tip of the device.

PRIORITY FROM RELATED APPLICATION

Priority is hereby claimed from U.S. Provisional Application Ser. No.60/566,776, filed Apr. 29, 2004, which is incorporated by referenceherein in its entirety.

BACKGROUND OF THE INVENTION

The eye is a complex organ with a variety of specialized tissues thatprovide the optical and neurological processes for vision. Accessing theeye for medical treatment is hindered by the small size and delicatenature of the tissues. Surgical access must not affect the opticalclarity or alignment of the tissues in the visual axis to preservevision. In addition, the eye is immunologically privileged, rendering itsusceptible to severe infection, especially when the intraocular spaceis challenged by both pathogens and trauma.

Minimally invasive surgical methods to access and treat tissues of theeye are desired to minimize trauma and introduction of pathogens.Dissection of the eye during surgery may affect the optical alignment oftissues involved in vision and typically results in scarring which makessubsequent surgery more difficult. Minimally invasive surgical methodsare advantageous in that they minimize potential alterations to theoptical alignment of the tissues in the visual axis. Minimally invasivesurgical methods may also allow for the use of small incisions, therebylimiting scarring and allowing subsequent surgical procedures to beperformed.

Minimally invasive methods are routinely used in eye surgery to treatcataracts. Small incisions are made into the cornea and appropriatelysized tools introduced and used under direct visualization through thecornea with a surgical microscope. The tools are used to remove theopacified natural lens and replace it with an intraocular lens implant.Minimally invasive methods are also used in retinal surgery, involvingthe introduction of tools into the posterior chamber of the eye throughsmall incisions in the pars plana region of the sclera. Directvisualization through the cornea and visual axis with a surgicalmicroscope allows the surgeon to manipulate tools to treat the retinaand macula.

The present invention describes microsurgical tools and methods, whichenable minimally invasive surgical access to the eye from within thesuprachoroidal space. The suprachoroidal space is a virtual spacebetween the sclera and choroid, due to the close apposition of the twotissues from the intraocular pressure of the eye. Although thesuprachoroidal space is delicate in nature and is adjacent to numerouschoroidal blood vessels, the present invention provides a flexible,catheter-like tool that may be safely placed in the suprachoroidal spaceand maneuvered anteriorly to the region near the cilliary body as wellas posteriorly to the area of the retina and optic nerve. Such tools maybe used to surgically treat the uveal scleral drainage pathway toincrease aqueous outflow in the treatment of glaucoma, to surgicallytreat the macula and choroidal vasculature in the treatment of maculardegeneration as well as to deliver drugs to the posterior tissues of theeye in the treatment of macular degeneration or optic nerve damage.

SUMMARY OF THE INVENTION

The present invention provides a composite microcannula device withproximal and distal ends for access and advancement within thesuprachoroidal space of the eye comprising, a flexible tubular sheathhaving an outer diameter of up to about 1000 microns and configured tofit within the suprachoroidal space of the eye; a proximal assemblyconfigured for introduction and removal of materials and tools throughthe proximal end; and a signal-producing beacon at the distal end tolocate the distal end within the eye, wherein the signal-producingbeacon is detectable visually or by non-invasive imaging.

The signal-producing beacon may be configured to emit visible light atan intensity that is visible externally through interposing tissues orthe beacon may comprise markers identifiable by non-invasive imaging,such as, ultrasound imaging, optical coherence tomography oropthalmoscopy. The marker, for example may be an optical contrastmarker. The beacon may provide illumination from the distal end at anangle of about 45 to about 135 degrees from the axis of the device to becoincident with the area of intended tissue treatment.

The tubular sheath is preferably curved in the range of 12 to 15 mmradius and may accommodate at least one additional signal-producingbeacon detectable visually or by non-invasive imaging to aid in judgingplacement and location. Typically, the sheath comprises a lubriciousouter coating and may have an atraumatic distal tip. The devicepreferably has a minimum length in the range of about 20 to about 30 mmto reach the posterior region of the eye from an anterior dissectioninto the suprachoroidal space.

The device may comprise an optical fiber for imaging tissues within oradjacent to the suprachoroidal space and an energy-emitting source fortreating blood vessels within or adjacent to the suprachoroidal space.The source may be capable, for example, of emitting laser light, thermalenergy, ultrasound, or electrical energy. Preferably the source isaligned with the location of the beacon to facilitate tissue targeting.

The device may further comprise an implant deliverable at the distalend. The implant may comprise a space-maintaining material or a drug.

The device may further comprise a sustained release drug formulationdeliverable at the distal end.

In another embodiment, the device additionally comprises an inner memberwith a proximal end and a distal end, wherein the sheath and innermember are sized such that the inner member fits slidably within thesheath and the distal end of the inner member is adapted to providetissue treatment to the eye through one or more openings in the distalend. The distal end of the inner member may be adapted for tissuedissection, cutting, ablation or removal. The inner member may be curvedin the range of 12 to 15 mm radius and may comprise a multi-lumen tubeand/or an optical fiber. The inner member may be made of steel, nickeltitanium alloy or tungsten.

In another embodiment, a composite microcannula device is provided forimplantation in the suprachoroidal space of an eye for delivery offluids to the posterior region of the eye comprising, a flexible tubularsheath having proximal and distal ends with an outer diameter of up toabout 1000 microns configured to fit within the suprachoroidal space ofthe eye; a self-sealing proximal fitting capable of receiving injectionsof fluids into the device, wherein the distal end of the sheath isadapted for release of fluids from the device into the eye.

The device may comprise a signal-producing beacon to locate the distalend within the suprachoroidal space during implantation wherein thesignal-producing beacon is detectable visually or by non-invasiveimaging. The device may be adapted for slow release of fluids, such asdrugs, from the distal end.

In another embodiment, a method is provided for treating thesuprachoroidal space of an eye comprising

a) inserting a flexible tubular sheath having proximal and distal endsand an outer

-   -   diameter of up to about of 1000 microns and an atraumatic distal        tip into the suprachoroidal space;

b) advancing the sheath to the anterior region of the suprachoroidalspace; and

c) delivering energy or material from the distal end to form a space foraqueous humor drainage.

The energy may comprise mechanical, thermal, laser, or electrical energysufficient to treat or remove scleral tissue in the vicinity of thedistal end. The material may comprise a space-maintaining material.

In another embodiment, a method is provided for treating the posteriorregion of an eye comprising

a) inserting a flexible tubular sheath having proximal and distal endsand an outer diameter of up to about 1000 micron into the suprachoroidalspace;

b) advancing the sheath to the posterior region of the suprachoroidalspace; and

c) delivering energy or material from the distal end sufficient to treatthe macula, retina, optic nerve or choroid.

The energy may comprise mechanical, thermal, laser, or electrical energysufficient to treat tissues in the vicinity of the distal end. Thematerial may comprise a drug or a drug and hyaluronic acid. The drug maycomprise a neuroprotecting agent, an anti-angiogenesis agent and/or ananti-inflammatory agent. A typical anti-inflammatory agent comprises asteroid.

In another embodiment, a method is provided for treating the tissueswithin or adjacent to the suprachoroidal space of an eye comprising

a) inserting a composite flexible microcannula device having proximaland distal ends and an outer diameter of up to about 1000 microns intothe suprachoroidal space, the device comprising an atraumatic distal tipand an optical fiber to provide detection of tissues in the vicinity ofthe distal tip;

b) advancing the device to the posterior region of the suprachoroidalspace;

c) detecting and characterizing tissues in the suprachoroidal space toidentify target tissues; and

d) delivering energy from the distal end to treat the target tissues.

The energy may comprise laser light, thermal, ultrasound or electricalenergy.

Typical target tissues comprise blood vessels.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a diagram of a flexible microcannula device according to theinvention.

FIG. 2 is a diagram of a microcannula device with a reinforcing memberaccording to the invention.

FIG. 3 is a diagram of a microcannula device having a signal-emittingbeacon at the distal tip according to the invention.

FIG. 4 shows of a microcannula device according to the inventionpositioned within the suprachoroidal space of the eye.

FIG. 5 shows a microcannula device according to the invention positionedwithin the suprachoroidal space and receiving a charge of drugsdelivered to the posterior region of the eye through the distal end.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides tools, materials and related methods tosurgically access the suprachoroidal space of an eye for the purpose ofperforming minimally invasive surgery or to deliver drugs to the eye.Specifically, the invention provides a flexible microcannula device thatmay be placed into the suprachoroidal space through a small incision ofthe overlying tissues, maneuvered into the appropriate region of thespace, and then activated to treat tissues adjacent to the distal tip ofthe device. The device may also include features for treating tissuesadjacent a region along the length of the device. The treatmentsaccomplished by the invention include mechanical modification ofadjacent tissues, the delivery of energy to adjacent tissues, thedelivery of drugs or drug delivery materials from the distal end of thedevice, or the delivery of an implant.

Referring to FIG. 1, a microcannula device is shown comprising aflexible elongated element 1 in the form of a tubular sheath with aconnector at the proximal end 2, a distal tip 3, and a communicatingchannel 4. The communicating channel 4 may be used to deliver fluids,drugs, materials, energy, gases, suction, surgical tools and implantsfrom the microcannula or the proximal connector to a distal site for avariety of tasks. The communicating channel 4 may be the lumen of atubular elongated element to transport materials, a fiber optic totransport light energy, or a wire to transport electrical signals. Amicrocannula of the present invention may comprise one or more elongatedelements, each having one or more communicating channels. In oneembodiment, the microcannula may consist of two or more elongatedelements with a reinforcing member to form a composite structure. Thecomponents may be adhered together, nested coaxially, or placed withinan outer sheath, such as heat shrink tubing. One of the elements may beused for transport of materials, another for transport of light orenergy, thus providing a multifunctional surgical tool.

Each elongated element may comprise a thin walled polymer or metal tubeof sufficient stiffness to allow it to be advanced along thesuprachoroidal space, but it should be flexible at least at its distalend. The proximal connector 2 may be of a ILuer type or similar systemfor the attachment or introduction of secondary elements or may bedesigned for attachment to specific components. To minimize the size ofthe suprachoroidal space occupied by the microcannula device it shouldbe appropriately sized. The device can have an outer diameter up toabout 1000 microns. Typically, the microcannula device is sized in therange of about 50 to about 1000 microns outer diameter with a wallthickness from about 10-200 microns. The cross-section of themicrocannula device may be round or ovoid to approximate the shape ofthe suprachoroidal space.

In one embodiment, a predetermined curvature may be applied to themicrocannula device to approximate the curvature of the eye, thecurvature being in the range of 12 to 15 mm radius. The length of themicrocannula is preferred to be long enough to reach the posteriorregion of the suprachoroidal space from an anterior access point,approximately 20 to 30 mm. Suitable materials for the elongated elementinclude metals, polymers such as polyetheretherketone (PEEK), polyimide,polyamide or polyether-block co-polyamide (Pebax), polysulfone,fluoropolymers, polypropylene, polyethylene or similar materials.Preferred materials for the sheath include polyamide, polyimide,polyether block amide, polyethylene terephthalate, polypropylene,polyethylene or fluoropolymer. The microcannula device may also comprisesurface treatments such as lubricious coatings or markings on theexterior for assessment of depth in the suprachoroidal space.

In one embodiment the microcannula comprises an inner member which fitsand slides within the elongated element, the inner member having aproximal end and a distal tip. Advancement or withdrawal of the innermember may be used to change the shape of the distal tip of themicrocannula, or alternatively to effect a mechanical action at thedistal tip to manipulate tissues or deliver an implant.

The microcannula of the present invention incorporates features thatenable it to be placed into and maneuvered in the suprachoroidal space.A key feature is to have the appropriate combination of axial stiffnessand compliance. To achieve this, referring to FIG. 2, it may be requiredto use a reinforcing element 5 attached to an elongated element 6,allowing smaller overall wall thickness of the element 6 to maximize thecross-sectional dimension of the communicating channel. The reinforcingelement may comprise any high modulus material such as metals includingstainless steel, titanium, cobalt chrome alloys, tungsten and nickeltitanium alloys, ceramic fibers and high strength polymer composites.The reinforcing element may comprise wires, coils or similarconfigurations. The reinforcing element or multiple elements may also beconfigured to provide a preferred deflection orientation of themicrocannula. The reinforcing element may also be a malleable materialsuch as a metal, to allow the surgeon to set a preferred geometry.

For optimal use in the suprachoroidal space, the microcannula ispreferred to be flexible at the distal end, but transitioning to morerigid mechanical compliance toward the proximal end. The transition maycomprise one or more steps in mechanical compliance, or a gradient ofcompliance along the length of the microcannula. It is also preferredthat the distal tip of the device be atraumatic. The distal tip mayincorporate a rounded shape or comprises a highly flexible material toprevent tissue damage during advancement of the device within thesuprachoroidal space. The microcannula may also incorporate mechanicalelements along its length to direct the shape and orientation of thedistal tip, allowing the surgeon to steer the microcannula while placingit in the suprachoroidal space.

An important feature of the device is the capability of being visualizedwithin the suprachoroidal space to allow guidance by the surgeon. Theuse of high resolution, non-invasive medical imaging, such as highfrequency ultrasound imaging, optical coherence tomography (OCT), orindirect opthalmoscopy, may be used in conjunction with the microcannuladevice of the invention. The patient eye may be imaged to determinesuitable avascular sites on the overlying tissues for introduction ofthe device. The suprachoroidal space may also be imaged to determine thebest regions for introducing or advancing the microcannula device tominimize potential trauma. The use of an ultrasound or optical contrastagent, either delivered directly to the suprachoroidal space orsystemically to the subject, may facilitate imaging. Material selectionand the use of contrast markers at the distal end and along the lengthof the microcannula device may be utilized to provide the desiredimaging properties for the device and facilitate image guidance.

Visualization of the microcannula in-situ may also be accomplished bydirect imaging via an endoscope placed in the suprachoroidal space. Aflexible endoscope may be used to track alongside the microcannula as itadvances. The endoscope should be constructed on a similar size scale tothe microcannula and may be a separate device used in conjunction withthe microcannula or fabricated as part of the microcannula. In oneembodiment of the invention, an imaging element such as a fiber opticbundle or gradient index lens imaging rod is fabricated to be co-linearwith the elongated element, creating a device with an oval crosssection. Due to the shape of the suprachoroidal space, the long axis ofthe combined device may be significantly larger in dimension than theshort axis, as long as the long axis is maintained parallel to thesurface of the scleral and choroidal tissues during advancement.

A signal-emitting beacon incorporated into the microcannula enhancesguidance of the device. Referring to FIG. 3, the microcannula 9 isfitted with a signaling beacon 7 to identify the location of themicrocannula distal tip 8 relative to the target tissues. The signalingbeacon 7 may be compatible with medical imaging techniques used to guidethe surgical procedure, or it may be made for direct visualization bythe surgeon. For example, the beacon 7 may comprise an echogenicmaterial for ultrasound guidance, an optically active material foroptical guidance or a light source for visual guidance.

In one embodiment, a plastic optical fiber (POF) may be incorporated toprovide a bright visual light source at the distal tip 8. The distal tipof the POF is positioned near or slightly beyond the end of the sheathof the microcannula and the emitted signal may be detected visuallythrough either the scleral tissues on the outside of the eye or throughthe choroidal tissues and the pupillary aperture. Such a signalingbeacon allows the distal end to be placed by the surgeon into thesuprachoroidal space and advanced under visual guidance through thesclera to confirm proper introduction and placement. The microcannulamay then be advanced within the suprachoroidal space to the area ofdesired tissue treatment under direct visualization. For treatment ofposterior regions of the eye, the signaling beacon may be visualizedthrough the papillary aperture and directed to the desired area. The POFmay also comprise a tip which is beveled, mirrored or otherwiseconfigured to provide for a directional beacon. A directional beacon maybe configured in the range of about 45 to about 135 degrees from themicrocannula axis to align with the direction and region of tissuetreatment from the distal end of the device. The beacon may beilluminated by a light source 10, such as a laser, laser diode,light-emitting diode, or an incandescent source such as a mercuryhalogen lamp. The beacon may also extend the along the length of themicrocannula to indicate the orientation of the microcannula to aidsurgical placement.

The microcannula device may be used to perform surgery at the distal endof the device. The distal end of the device may incorporate elementsthat allow for therapeutic intervention to the tissues. For example, thedistal end may be advanced near the anterior region of thesuprachoroidal space and the device activated to treat tissues adjacentto the distal tip. The tissue treatment may comprise the cutting orremoval of tissues to form a cyclodialysis cleft, the ablation oftissues to enhance uveal scleral drainage or the placement of an implantto increase uveal scleral drainage. The distal end may also be advancedto any region of the suprachoroidal space requiring treatment of thechoroids, macula, or retina. The tissue treatment may comprise theapplication of suction to drain suprachoroidal hemorrhage or choroidaleffusion, or the treatment of the optic nerve sheath to relieve retinalvein occlusion. The tissue treatment may also comprise the applicationof energy or surgical tools to treat choroidal neovscularization,melanoma or nevus. Various forms of energy application may beaccomplished using suitably adapted microcannulae, including laser,electrical such as radio frequency ultrasound, thermal and mechanicalenergy. In such a case, the device additionally comprises an innermember with a proximal end and a distal end, wherein the sheath of themicrocannula and inner member are sized such that the inner member fitsslidably within the sheath and the distal end of the inner member isadapted to provide tissue treatment to the eye through one or moreopenings in the distal end. The distal end of the inner member may beadapted for tissue dissection, cutting, ablation or removal. The innermember may be curved in the range of 12 to 15 mm radius and may comprisea multi-lumen tube and/or an optical fiber. The inner member may be madeof steel, nickel titanium alloy or tungsten.

In one embodiment of the invention, the microcannula device incorporatesimaging element to allow the surgeon to view, characterize, and treatblood vessels from the suprachoroidal space. For example, the device mayincorporate an endoscope to image the local tissues and blood vessels.The imaging may incorporate non-visual wavelengths of light such asinfra-red to aid tissue penetration. When energy is delivered by themicrocannula, the area of energy delivery may be aligned to coincidewith a specific area of the imaging means to facilitate specific tissuetargeting by the surgeon. The imaging may also include elements tocharacterize blood flow, such as Doppler flow methods, to identifytarget vessels for treatment. The treatment method may also incorporatethe use of localized labeling of target vasculature with photosensitiveagents such as used in photodynamic therapy. After characterization andidentification of target blood vessels, the microcannula may be used todeliver energy such as laser light or radio frequency energy to thevessels to reduce neovascularization or blood vessel leakage.

The microcannula may also be used to deliver drugs or drug deliveryimplants from the distal end of the device. Referring to FIG. 4, themicrocannula 11 may be advanced in the suprachoroidal space to theposterior pole 12 via a surgical entry point 12A formed by a surgicalformed scleral flap 12B. The microcannula may be used to deliver drugsor drug delivery implants to the target site. The drug or drugcontaining material may be delivered either from a storage space in themicrocannula or by transport from a proximal connector 2 (FIG. 1)through a lumen of the microcannula. Drug containing materials thatprovide sustained release over time are of particular utility. Thematerials may be delivered near the optic nerve to treat nerve damagefrom glaucoma, or delivered in the suprachoroidal space to treatchoroidal or retinal diseases, including macular degeneration, macularedema, retinopathy, or cancer. In one embodiment, the microcannula isused to deliver microparticles of drug to the suprachoroidal space toprovide a sustained release of drug to diseased tissues. Themicrocannula must be appropriately sized, with a lumen dimension of fiveto ten times the mean size of the drug microparticles, with a smoothflow path to prevent obstruction by the microparticles. Themicroparticles may be formulated into a suspension and injected throughthe microcannula at the appropriate location of the eye to providehighly localized drug concentration. A typical drug formulation maycomprise drug microparticles suspended in a hyaluronic acid solution.The drug may also be delivered to the suprachoroidal space as a soliddosage form, either in the form of microparticles, a filament or a drugreleasing implant designed to reside in the suprachoroidal space.

Referring to FIG. 5, a microcannula 13 is designed as a permanentimplant, residing in the suprachoroidal space 14. The distal end 15 ofthe microcannula is adapted to deliver drugs 16 over a sustained periodto the posterior region of the eye. The distal end may incorporatemicroporosity or diffusional barriers to provide the appropriate drugrelease kinetics. The proximal end 17 of the microcannula is implantedto extend outside of the suprachoroidal space, and is positioned withinthe sclera or into the subconjunctival space. The proximal end 17incorporates a self-sealing septum (not shown) that allows repeatedinjection into the device with a syringe 18 to refill the device withdrug. The proximal end 17 may be placed in the anterior region of theeye to facilitate access. The distal end 15 may be positioned near theoptic nerve or the region of retina or macula to be treated. The devicemay be used to provide sustained delivery of drugs such asneuroprotectants to treat damage to the optic nerve, anti-angiogenesisagents to treat macular degeneration and anti-inflammatory agents totreat inflammation in the posterior segment of the eye. The microcannulaimplant may also contain space-maintaining materials, such as hyaluronicacid. Also, the implant may be provided with a signal-producing beaconto locate the distal end within the suprachoroidal space duringimplantation. The microcannula of this embodiment is preferablyconstructed from materials suitable for implantation in soft tissues.Such materials include polymers such as polydimethylsiloxane,polyurethanes, Teflon, silicone-urethane copolymers, polyether-blockco-polyamide, polyamide, and polyamide. The implant microcannula mayalso utilize secondary elements such as an outer or inner microcannulato facilitate surgical implantation. The outer surface of the implantmicrocannula may also incorporate features for in situ mechanicalsecurement, such as tissue ingrowth porosity or features for sutureanchoring.

The invention also provides methods to treat an eye by surgicallyaccessing the suprachoroidal space. The following methods are providedas explanatory and do not constitute the entire scope of methods whichmay be used in conjunction with the devices described herein. In a firstexample, the surgeon accesses the suprachoroidal space and places amicrocannula device having an atraumatic distal end within the space. Amicrocannula device comprising a sheath with an inner member and beaconsignal is used, wherein the inner member has a distal tip configured totreat or excise tissue. The device is advanced within the space whilevisualizing the beacon signal to position the device tip to a locationdesired for surgical treatment. The device is actuated to treat acontrolled amount of tissues adjacent to the distal tip. The energy maycomprise mechanical, thermal, laser, or electrical energy sufficient totreat or remove scleral tissue in the vicinity of the distal end. Thesurgical treatment may include: formation of a space for aqueous humordrainage; treatment of the macula, retina, optic nerve or choroids inthe posterior region of the suprachoroidal space; treating blood vesselswithin or adjacent to the suprachoroidal space. To treat blood vessels,the device preferably is adapted with an optical fiber to provide thecapability of detecting and characterizing tissues and identifyingtarget vessels before delivery of the treatment. After the surgicaltreatment, the device is removed and the access site is then sealed byany requisite method.

In another embodiment, the suprachoroidal space is surgically accessedand a microcannula device placed within the space. A microcannula devicecomprising a tubular sheath incorporating a beacon signal at the distalend is used. The device is advanced within the suprachoroidal spacewhile visualizing the beacon signal first through the scleral tissuesand second through the papillary aperture to position the device tip toa posterior location desired for drug treatment. Drugs, drug-containingmaterials or space-maintaining materials are delivered through themicrocannula. The device is removed and the access site is then sealedby any requisite method.

The procedure may also be performed at more than site per eye as may berequired. In practice, the procedure may be performed on one or moresites, and the patient monitored post-surgically. If more treatment isrequired, then a subsequent procedure may be performed.

The following examples are presented for the purpose of illustration andare not intended to limit the invention in any manner.

EXAMPLE 1

A microcannula comprising a polyimide infusion lumen, a stainless steelanti-kink core wire and a plastic optical fiber to create a beaconsignal at the device tip was fabricated. The components were boundtogether using very thin walled heat shrink tubing of polyethyleneterephthalate (PET). The assembled microcannula was approximately 200microns in outer diameter, 75 microns inner diameter and with a workinglength of 25 mm. An atraumatic ball-shaped distal tip was produced byheating the end of the PET shrink tubing to it's melt point prior toassembly. The surface tension of the melt results in the creation of arounded ball-shaped tip. A stainless steel wire was placed in the lumento maintain the lumen during the melting of the tip. The proximal endconsisted of an infusion tube connected to a luer fitting, and a fiberoptic light pipe connected to a 25 mW laser diode illumination source.The luer fitting was attached to an injector filled with a surgicalviscoelastic (Healon GV, Advanced Medical Optics, Irvine, Calif.).

Enucleated human eyes were prepared for surgery. Using a radial orradial plus lateral (cross) incision, the sclera was cut down to thesuprachoroidal space above the medial rectus muscle attachment near thepars plana. After accessing the suprachoroidal space, the microcannulawas advanced into the space while visually observing the beacon signalat the tip. The beacon tip could be observed from the outside of the eyethrough the overlying sclera, and also from the inside of the eyethrough the interposing choroidal tissues. The tip of the device couldbe positioned by manipulation of the proximal end while observing thebeacon signal at the device distal tip. With the microcannula directedposteriorly, the device was able to be advanced adjacent to the opticnerve. Directed laterally, the device could be advanced completelyaround the globe, tracking a great circle route. Directed anteriorly,the device could be advanced into Schlemm's Canal and then into theanterior chamber. In a second experiment, the microcannula was placedinto the suprachoroidal space under guidance with a high frequencyultrasound imaging system. The microcannula could be observed and guidedwithin the suprachoroidal space under imaging. An injection ofviscoelastic was made while observing the site with the imaging systemshowing a viscoelastic dissection of the space in the area of themicrocannula distal tip.

EXAMPLE 2

A drug formulation was prepared for suprachoroidal administration byinjection through a microcannula of the present invention. Threemilliliters of sterile triamcinolone acetonide suspension (Kenalog 40,40 mg/ml, Bristol Meyers Squib) was withdrawn into a sterile syringe.The syringe was attached to a sterile 0.45 micron syringe filter and thedrug suspension was injected into the filter, capturing the drugparticles. A second syringe with an adjunct mixer was attached to thefilter and 0.6 milliliters of sterile hyaluronic acid solution (Healon,10 mg/ml, Advanced Medical Optics, Irvine, Calif.) introduced into thefilter containing the drug particles. The hyaluronic acid and drugparticles were then withdrawn into the first syringe and the filterremoved. The hyaluronic acid and drug particles were mixed by multiplepassage between two sterile syringes. The suspended drug formulationcontained 200 mg/ml triamcinolone acetonide and 10 mg/ml hyaluronicacid. The drug formulation was then transferred to a viscoelasticinjector for injection through a microcannula. The mean particle size ofthe triamcinolone acetonide suspended in hyaluronic acid solution wasmeasured using a Coulter Counter instrument, demonstrating a meanparticle size of approximately 4 microns.

EXAMPLE 3

Microcannulae were fabricated, comprising a communicating element of 65Shore D durometer Pebax tubing of 0.008″×0.0010″ diameter, containing aplastic optical fiber 0.0033″ diameter and a stainless steel wire 0.001″diameter within the lumen. The plastic optical fiber was connected to alaser diode light source similar to that used in Example 1 to providefor an illuminated beacon distal tip. The steel wire was incorporated toprevent kinking of the shaft. The lumen of the tube was attached to alarger plastic tube and then to a proximal Luer connector for theattachment of a syringe or viscoelastic injector. An atraumatic distaltip was created by applying a small amount of high viscosity ultravioletcure adhesive and allowing the surface tension to create a ball-shapedtip prior to curing. The devices were sterilized for use by gammairradiation.

Animal studies were performed to evaluate the microcannula in accessingthe suprachoroidal space and advancing to the posterior pole. The studywas performed using juvenile farm pigs. In each surgery, the animalswere anesthetized and prepared per standard ophthalmic surgicalprocedures. A limbal perotomy was performed to retract the conjunctiva.A small scleral incision was made in the pars plana region down to thechoroid layer. The microcannula was inserted into the incision to accessthe suprachoroidal space and then advanced back to the posterior pole.Surgical microscope visualization through the pupillary apertureindicated the location of the microcannula distal tip by observing theilluminated beacon tip. The microcannula could be advanced to theposterior region of the eye without difficulty or visible tissue trauma.

EXAMPLE 4

Microcannulae similar to those used in Example 3 were made without theatraumatic tip. The devices were used during the porcine animal study asdetailed in Example 3. In one case, the microcannula was unable to beadvanced into the posterior region, appearing to be caught on thetissues of the suprachoroidal space. In a second case, the microcannulawas able to advance to the posterior pole, but was seen to catch on thechoroidal tissues in a number of locations, causing tissueirregularities visible upon angiographic imaging. In the remainingtrials, the microcannulae without atraumatic tipping were able to beadvanced in the suprachoroidal space. It was noted in each case that thedevices were more difficult to advance than those with an atraumatictip.

EXAMPLE 5

Microcannulae were fabricated and used in porcine animal studies asdescribed in Example 3.

A viscoelastic (Healon, Advanced Medical Optics, Irvine, Calif.) or asteroid/viscoelastic (triamcinilone acetonide plus Healon) formulationas described in Example 2 was delivered to the suprachoroidal space inthe region of the area centralis. Viscoelastic and steroid/viscoelasticdelivery amounts ranged from 1.2 to 9.2 mg. The delivered materialscould be observed in the suprachoroidal space by direct visualizationand by posterior segment imaging using a scanning laser opthalmoscope.Animals were survived up to one month. Posterior segment imaging atsacrifice did not show any observable changes to the retinal orchoroidal blood flow, and no adverse tissue reactions were seen.

EXAMPLE 6

A flexible microcannula comprising a small endoscope was fabricated foruse in the suprachoroidal space. An experiment was performed to evaluatethe use of the microcannula for direct imaging of the scleral andchoroidal tissues from within the suprachoroidal space. A custommicro-endoscope (Nanoptics Inc., Gainesville, Fla.) consisting of about3000 glass fibers was fabricated. The micro-endoscope had an externaljacket dimension of about 250 microns terminating in a 350 microndiameter tip that included a gradient lens objective with a 5 mm focus.The micro-endoscope was coupled via a 10× Mitutoyo microscope objectiveand tube lens to a CCD video camera, and then to a video monitor.

An enucleated human cadaver eye was used for the experiment. A radialincision at the pars plana was made to the depth of the choroid. A smallamount of viscoelastic (Healon GV, Advanced Medical Optics, Irvine,Calif.) was injected into the surgical incision to open thesuprachoroidal space for placement of the micro-endoscope and tolubricate the passage. The micro-endoscope was inserted into theincision and advanced posterior in the suprachoroidal space.Transillumination was provided by the surgical microscope, which wasadjusted to provide the best image without saturating the camera image.The micro-endoscope was advanced and manipulated to view variouslocations within the space. The tissues could be easily identified, thesclera appeared as a white colored bright tissue (due to thetransillumination) and the choroid appeared dark reddish brown withdetails of the choroidal surface discernable.

EXAMPLE 7

An indwelling microcannula implant to provide repeated access to thesuprachoroidal space was fabricated. The microcannula comprised Pebaxpolymer tubing 0.010″ ID×0.012″ OD. An atraumatic distal tip was createdby applying a high viscosity ultraviolet cure adhesive to the tubingend, thus forming a rounded tip. A tissue interfacing flange was createdat the proximal end by applying heat to the end of the tube, causing itto flare outwards. The total length of the microcannula was 0.79″. Theindwelling microcannula was placed over a delivery microcannula similarto the microcannula of Example 1 with a 4″ working length. The deliverymicrocannula was 0.008″ OD and contained a plastic optical fiber toprovide for an illuminated distal tip. The proximal end of the fiber wasconnected to a battery powered laser diode source as described inExample 1. The delivery microcannula was sized to fit snugly inside theindwelling microcannula.

An enucleated human cadaver eye was used for the experiment. A radialincision at the pars plana was made, the incision going through thesclera and exposing the choroid. A small amount of viscoelastic fluid(Healon, Advanced Medical Optics, Irvine, Calif.) was injected into thesuprachoroidal space at the incision in order to dissect the choroidfrom the sclera sufficiently to allow placement of the microcannula.

The laser diode was activated, providing a red light beacon tip on thedelivery microcannula. The assembly was placed into the suprachoroidalspace and advanced under visual guidance toward the posterior pole. Theassembly was advanced until the tissue flange of the indwellingmicrocannula was flush with the scleral surface. Examination of theexterior of the eye showed the beacon tip was located near the macularregion.

The delivery microcannula was withdrawn, while holding the indwellingmicrocannula in place with a pair of forceps. The incision was sealedwith cyanoacrylate adhesive. Using a 1 cc syringe, a small amount ofmethylene blue dye was injected into the exposed lumen of the indwellingmicrocannula using a 31 gauge hypodermic needle. After completion of theinjection, a small incision was made through the sclera at the macularregion near the distal tip of the microcannula. Methylene blue dye wasseen at this incision confirming the delivery of the injection to theposterior region of the suprachoroidal space from an injection into theproximal end of the microcannula located in the anterior region.

1. A composite microcannula device with proximal and distal ends foraccess and advancement within the suprachoroidal space of the eyecomprising, a flexible tubular sheath having an outer diameter of up toabout 1000 microns and configured to fit within the suprachoroidal spaceof the eye; a proximal assembly configured for introduction and removalof materials and tools through said proximal end; and a signal-producingbeacon at said distal end to locate said distal end within the eye,wherein said signal-producing beacon is detectable visually or bynon-invasive imaging.
 2. A device according to claim 1 wherein saidsignal-producing beacon is detectable in the suprachoroidal space, theinterposing scleral tissue external to the suprachoroidal space, and theinterposing choroidal tissue internal to the suprachoroidal space.
 3. Adevice according to claim 2, wherein said signal-producing beacon isconfigured to emit visible light at an intensity that is visibleexternally through said interposing tissues.
 4. A device according toclaim 1, wherein said signal-producing beacon comprises markersidentifiable by non-invasive imaging.
 5. A device according to claim 4,wherein said non-invasive medical imaging comprises ultrasound imaging,optical coherence tomography or opthalmoscopy.
 6. A device according toclaim 4 wherein said markers comprise an optical contrast marker.
 7. Adevice according to claim 1 wherein said tubular sheath is curved in therange of 12 to 15 mm radius.
 8. A device according to claim 1 whereinsaid tubular sheath accommodates at least one additionalsignal-producing beacon detectable visually or by non-invasive imagingto aid in judging placement and location.
 9. A device according to claim1 wherein said tubular sheath comprises polyamide, polyimide, polyetherblock amide, polyethylene terephthalate, polypropylene, polyethylene orfluoropolymer.
 10. A device according to claim 1 wherein said tubularsheath comprises a lubricious outer coating.
 11. A device according toclaim 1 wherein said tubular sheath comprises an atraumatic distal tip.12. A device according to claim 1 having a minimum length in the rangeof about 20 to about 30 mm to reach the posterior region of the eye froman anterior dissection into the suprachoroidal space.
 13. A deviceaccording to claim 1 further comprising an implant deliverable at saiddistal end.
 14. A device according to claim 13 wherein said implantcomprises a space-maintaining material.
 15. A device according to claim13 wherein said implant comprises a drug.
 16. A device according toclaim 1 further comprising a sustained release drug formulationdeliverable at said distal end.
 17. A device according to claim 16wherein said drug formulation comprises microparticles.
 18. A deviceaccording to claim 17 wherein said microparticles are suspended in ahyaluronic acid solution.
 19. A device according to claim 1 additionallycomprising an inner member with a proximal end and a distal end, whereinsaid sheath and inner member are sized such that said inner member fitsslidably within said sheath and said distal end of said inner member isadapted to provide tissue treatment to the eye through one or moreopenings in said distal end of said device.
 20. A device according toclaim 19 wherein said distal end of said inner member is adapted fortissue dissection, cutting, ablation or removal.
 21. A device accordingto claim 19 wherein said inner member is curved in the range of 12 to 15mm radius.
 22. A device according to claim 19 wherein said inner membercomprises a multi-lumen tube.
 23. A device according to claim 19 whereinsaid inner member comprises steel, nickel titanium alloy or tungsten.24. A device according to claim 19 wherein said inner member comprisesan optical fiber.
 25. A device according to claim 1 or 19 wherein saidbeacon provides illumination from the distal end of said device at anangle of about 45 to about 135 degrees from the axis of said device tobe coincident with the area of intended tissue treatment.
 26. A deviceaccording to claim 1 further comprising an optical fiber for imagingtissues within or adjacent to the suprachoroidal space.
 27. A deviceaccording to claim 1 further comprising an energy-emitting source fortreating blood vessels within or adjacent to the suprachoroidal space.28. A device according to claim 27 wherein said source is capable ofemitting laser light, thermal energy, ultrasound, or electrical energy.29. A device according to claim 27 or 28 wherein said source is alignedwith the location of said beacon to facilitate tissue targeting.
 30. Acomposite microcannula device for implantation in the suprachoroidalspace of an eye for delivery of fluids to the posterior region of theeye comprising, a flexible tubular sheath having proximal and distalends with an outer diameter of up to about 1000 microns configured tofit within the suprachoroidal space of the eye; a self-sealing proximalfitting capable of receiving injections of fluids into said device,wherein said distal end of said sheath is adapted for release of fluidsfrom said device into the eye.
 31. A device according to claim 30further comprising a signal-producing beacon to locate said distal endwithin the suprachoroidal space during implantation wherein saidsignal-producing beacon is detectable visually or by non-invasiveimaging.
 32. A device according to claim 30 that is adapted for slowrelease of fluids from said distal end.
 33. A device according to any ofclaims 30 to 32 wherein said fluids comprise drugs.
 34. A method fortreating the suprachoroidal space of an eye comprising a) inserting aflexible tubular sheath having proximal and distal ends and an outerdiameter of up to about of 1000 microns and an atraumatic distal tipinto the suprachoroidal space; b) advancing said sheath to the anteriorregion of the suprachoroidal space; and c) delivering energy or materialfrom said distal end to form a space for aqueous humor drainage.
 35. Themethod according to claim 34 wherein said energy comprises mechanical,thermal, laser, or electrical energy sufficient to treat or removescleral tissue in the vicinity of said distal end.
 36. The methodaccording to claim 34 wherein said material comprises aspace-maintaining material.
 37. A method for treating the posteriorregion of an eye comprising a) inserting a flexible tubular sheathhaving proximal and distal ends and an outer diameter of up to about1000 micron into the suprachoroidal space; b) advancing said sheath tothe posterior region of the suprachoroidal space; and c) deliveringenergy or material from said distal end sufficient to treat the macula,retina, optic nerve or choroid.
 38. The method according to claim 37wherein said energy comprises mechanical, thermal, laser, or electricalenergy sufficient to treat tissues in the vicinity of said distal end.39. The method according to claim 37 wherein said material comprises adrug.
 40. The method according to claim 39 wherein said material furthercomprises hyaluronic acid.
 41. The method according to claim 39 whereinsaid drug comprises a neuroprotecting agent.
 42. The method according toclaim 39 wherein said drug comprises an anti-angiogenesis agent.
 43. Themethod according to claim 39 wherein said drug comprises ananti-inflammatory agent.
 44. The method according to claim 43 whereinsaid anti-inflammatory agent comprises a steroid.
 45. A method fortreating the tissues within or adjacent to the suprachoroidal space ofan eye comprising a) inserting a composite flexible microcannula devicehaving proximal and distal ends and an outer diameter of up to about1000 microns into the suprachoroidal space, said device comprising anatraumatic distal tip and an optical fiber to provide detection oftissues in the vicinity of said distal tip; b) advancing said device tothe posterior region of the suprachoroidal space; c) detecting andcharacterizing tissues in the suprachoroidal space to identify targettissues; and d) delivering energy from said distal end to treat saidtarget tissues.
 46. The method according to claim 45 wherein said energycomprises laser light, thermal, ultrasound or electrical energy.
 47. Themethod according to claim 45 wherein said target tissues comprise bloodvessels.